Amiodarone and the risk of cancer

Abstract

BACKGROUND:In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy. METHODS: Using the Taiwan National Health Insurance Research database, the authors conducted a population-based cohort study. Patients who were treated with amiodarone between 1997 and 2008 were enrolled. Those with antecedent cancer were excluded. Standardized incidence ratios (SIRs) of cancers were calculated to compare the cancer incidence of the study cohort with that of the general population. A multivariate Cox regression model was used to evaluate the association between cumulative defined daily doses (cDDDs) of amiodarone and cancer occurrence. RESULTS: The study included 6418 subjects, with a median follow-up of 2.57 years. A total of 280 patients developed cancer. The risk of cancer increased with borderline significance (SIR, 1.12; 95% confidence interval [95% CI], 0.99-1.26 [P ¼ .067]). Male patients had a higher risk (SIR, 1.18; 95% CI, 1.02-1.36 [P ¼ .022]). The total cohort of patients and the male patients with > 180 cDDDs within the first year were found to have SIRs of 1.28 (95% CI, 1.00-1.61; P ¼ .046) and 1.46 (95% CI, 1.11-1.89; P ¼ .008), respectively. After adjustment for age, sex, and comorbidities, the hazards ratio was 1.98 (95% CI, 1.22-3.22; P ¼ .006) for the high tertile of cDDDs compared with the low tertile. CONCLUSIONS: The results of the current study indicate that amiodarone may be associated with an increased risk of incident cancer, especially in males, with a dose-dependent effect.

Atrial Fibrillation and Risk of Cancer: A Danish Population‐Based Cohort Study

“…Antithrombotic treatment may also cause hematuria; however, only a small percentage of patients with macroscopic hematuria are diagnosed with prostate cancer 30. Second, other AF‐related treatments, such as amiodarone or digoxin, may also be associated with an increased risk of cancer,31, 32 and a causal relationship between AF per se and cancer may exist. However, both seem unlikely because of the strong association with metastatic cancer within 90 days, the initial sharp increase in the cumulative incidence of cancer, and the attenuation of the HRs over time, all of which suggest that cancer is already present at the time of the diagnosis of AF.…”

Amiodarone Therapy for Cardiac Arrhythmias: Is It Associated with the Development of Cancers?

“…The cancers associated with amiodarone treatment that were observed most in the Su et al [25] study occurred in the digestive tract, liver and biliary system, colon and rectum, and genitourinary system. However, thyroid cancers, skin cancers, and lung cancer-like masses are the most commonly reported in the literature to date.…”

“…There were 280 patients who developed cancers ( Table 3), Table 3. Specific cancer types found among the patients treated with amiodarone in the Su et al [25] study.…”

“…These reported thyroid cancers, whether associated with hyperthyroidism or hypothyroidism, developed following 2 -5 years of amiodarone therapy or within 1 year after amiodarone discontinuation. This suggests that the accumulation of high doses of amiodarone may be needed for the development of an associated cancer, and that a latency period may also be involved [25]. In all these cases, thyroid function improved following the discontinuation of amiodarone and the appropriate thyroid dysfunction treatment.…”

“…Recently, Su et al [25] performed a nationwide population-based cohort study in Taiwan to determine whether amiodarone treatment is associated with an increased risk of cancers. This was the first large scale study to focus its evaluations on the risk of cancers in patients treated with amiodarone.…”